VOXTALISIB

Details

Stereochemistry	ACHIRAL
Molecular Formula	C13H14N6O
Molecular Weight	270.2899
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCN1C(=O)C(=CC2=C1N=C(N)N=C2C)C3=CC=NN3

InChI

InChIKey=RGHYDLZMTYDBDT-UHFFFAOYSA-N

InChI=1S/C13H14N6O/c1-3-19-11-8(7(2)16-13(14)17-11)6-9(12(19)20)10-4-5-15-18-10/h4-6H,3H2,1-2H3,(H,15,18)(H2,14,16,17)

HIDE SMILES / InChI

Molecular Formula	C13H14N6O
Molecular Weight	270.2899
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/c |https://newdrugapprovals.org/2015/10/28/voxtalisib-hydrochloride-sar-245409-xl-765/
Curator's Comment: Description was created based on several sources, including http://www.selleckchem.com/products/XL765(SAR245409).html https://www.ncbi.nlm.nih.gov/pubmed/25300944

Voxtalisib (SAR245409, XL765) is an orally available inhibitor of PI3K and the mammalian target of rapamycin (mTOR), which are frequently activated in human tumors and play central roles in tumor cell proliferation. Exelixis discovered Voxtalisib internally and out-licensed the compound to Sanofi. Voxtalisib is being evaluated by Sanofi as a single agent and in multiple combination regimens in a variety of cancer indications. Clinical trials have included a single agent phase 2 trial in Non-Hodgkin’s lymphoma, combination phase 1b/2 trials with temozolomide in patients with glioblastoma, with letrozole in hormone receptor positive breast cancer, with bendamustine and/or rituximab in lymphoma or leukemia, and a phase 1 trial in combination with a MEK inhibitor. Voxtalisib is a highly selective, potent and reversible ATP-competitive inhibitor of pan-Class I PI3K (α, β, γ, and δ) and mTORC1/mTORC2. It is orally active, highly selective over 130 other protein kinases. In cellular assays, XL765 inhibits the formation of PIP3 in the membrane, and inhibits phosphorylation of AKT, p70S6K, and S6 phosphorylation in multiple tumor cell lines with different genetic alterations affecting the PI3K pathway.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
PI3-kinase p110-gamma subunit 32 Target ID: CHEMBL3267 Sources: https://pubs.rsc.org/en/content/articlelanding/2012/MD/c2md20044a#!divAbstract	Inhibitor 8297	9.0 nM [IC50]
PI3-kinase p110-delta subunit 43 Target ID: CHEMBL3130 Sources: https://pubs.rsc.org/en/content/articlelanding/2012/MD/c2md20044a#!divAbstract	Inhibitor 8297	43.0 nM [IC50]
PI3-kinase p110-alpha subunit 41 Target ID: CHEMBL4005 Sources: https://pubs.rsc.org/en/content/articlelanding/2012/MD/c2md20044a#!divAbstract	Inhibitor 8297	39.0 nM [IC50]
PI3-kinase p110-beta subunit 31 Target ID: CHEMBL3145 Sources: https://pubs.rsc.org/en/content/articlelanding/2012/MD/c2md20044a#!divAbstract	Inhibitor 8297	113.0 nM [IC50]
PI3-kinase p110-alpha subunit 41 Target ID: CHEMBL4005 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18794885	Inhibitor 8297	39.0 nM [IC50]
PI3-kinase p110-beta subunit 31 Target ID: CHEMBL3145 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18794885	Inhibitor 8297	113.0 nM [IC50]
PI3-kinase p110-gamma subunit 32 Target ID: CHEMBL3267 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18794885	Inhibitor 8297	9.0 nM [IC50]
PI3-kinase p110-delta subunit 43 Target ID: CHEMBL3130 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18794885	Inhibitor 8297	43.0 nM [IC50]
DNA-dependent protein kinase 11 Target ID: CHEMBL3142 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18794885	Inhibitor 8297	150.0 nM [IC50]
Serine/threonine-protein kinase mTOR 35 Target ID: CHEMBL2842 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18794885	Inhibitor 8297	157.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Lymphoma 58 Sources: https://clinicaltrials.gov/ct2/show/NCT01403636	Primary	Phase II 1132	Unknown Approved Use Unknown
Ovarian cancer 157 Sources: https://clinicaltrials.gov/ct2/show/NCT01936363	Primary	Phase II 1132	Unknown Approved Use Unknown
Breast cancer 434 Sources: https://clinicaltrials.gov/ct2/show/NCT01082068	Primary	Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
353 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28417284	40 mg 2 times / day multiple, oral dose: 40 mg route of administration: Oral experiment type: MULTIPLE co-administered:	VOXTALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
360 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28417284	60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered:	VOXTALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
416 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28417284	50 mg 2 times / day multiple, oral dose: 50 mg route of administration: Oral experiment type: MULTIPLE co-administered:	VOXTALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
541 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28417284	70 mg single, oral dose: 70 mg route of administration: Oral experiment type: SINGLE co-administered:	VOXTALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
395 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28417284	40 mg 2 times / day steady-state, oral dose: 40 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	VOXTALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
417 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28417284	70 mg 1 times / day steady-state, oral dose: 70 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	VOXTALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
549 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28417284	50 mg 2 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	VOXTALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
477 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28417284	60 mg 1 times / day multiple, oral dose: 60 mg route of administration: Oral experiment type: MULTIPLE co-administered:	VOXTALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
1920 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28417284	40 mg 2 times / day multiple, oral dose: 40 mg route of administration: Oral experiment type: MULTIPLE co-administered:	VOXTALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1950 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28417284	60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered:	VOXTALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2110 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28417284	50 mg 2 times / day multiple, oral dose: 50 mg route of administration: Oral experiment type: MULTIPLE co-administered:	VOXTALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3840 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28417284	70 mg single, oral dose: 70 mg route of administration: Oral experiment type: SINGLE co-administered:	VOXTALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1530 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28417284	40 mg 2 times / day steady-state, oral dose: 40 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	VOXTALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2190 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28417284	70 mg 1 times / day steady-state, oral dose: 70 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	VOXTALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3390 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28417284	50 mg 2 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	VOXTALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3700 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28417284	60 mg 1 times / day multiple, oral dose: 60 mg route of administration: Oral experiment type: MULTIPLE co-administered:	VOXTALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
2.72 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28417284	40 mg 2 times / day multiple, oral dose: 40 mg route of administration: Oral experiment type: MULTIPLE co-administered:	VOXTALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28417284	60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered:	VOXTALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4.33 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28417284	50 mg 2 times / day multiple, oral dose: 50 mg route of administration: Oral experiment type: MULTIPLE co-administered:	VOXTALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4.55 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28417284	70 mg single, oral dose: 70 mg route of administration: Oral experiment type: SINGLE co-administered:	VOXTALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.29 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28417284	40 mg 2 times / day steady-state, oral dose: 40 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	VOXTALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3.04 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28417284	70 mg 1 times / day steady-state, oral dose: 70 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	VOXTALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28417284	50 mg 2 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	VOXTALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28417284	60 mg 1 times / day multiple, oral dose: 60 mg route of administration: Oral experiment type: MULTIPLE co-administered:	VOXTALISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
120 mg 2 times / day multiple, oral Highest studied dose Dose: 120 mg, 2 times / day Route: oral Route: multiple Dose: 120 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24583798 Page: p.2447	unhealthy, ADULT n = 7 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/24583798 Page: p.2447	DLT: Hypophosphatemia, Decreased appetite... Other AEs: Hepatic enzyme increased... Dose limiting toxicities: Hypophosphatemia (grade 3, 14.3%) Decreased appetite (grade 3, 14.3%) Other AEs: Hepatic enzyme increased (42.9%) Sources: https://pubmed.ncbi.nlm.nih.gov/24583798 Page: p.2447
40 mg 2 times / day multiple, oral MTD Dose: 40 mg, 2 times / day Route: oral Route: multiple Dose: 40 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28417284 Page: p.4	unhealthy, ADULT n = 6 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/28417284 Page: p.4	DLT: Fatigue... Dose limiting toxicities: Fatigue (grade 3, 16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/28417284 Page: p.4
50 mg 2 times / day multiple, oral MTD Dose: 50 mg, 2 times / day Route: oral Route: multiple Dose: 50 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24583798 Page: p.2447	unhealthy, ADULT n = 25 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 25 Sources: https://pubmed.ncbi.nlm.nih.gov/24583798 Page: p.2447	DLT: Pruritic rash... Dose limiting toxicities: Pruritic rash (grade 2, 8%) Sources: https://pubmed.ncbi.nlm.nih.gov/24583798 Page: p.2447
60 mg 1 times / day multiple, oral MTD Dose: 60 mg, 1 times / day Route: oral Route: multiple Dose: 60 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28417284 Page: p.4	unhealthy, ADULT n = 15 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 15 Sources: https://pubmed.ncbi.nlm.nih.gov/28417284 Page: p.4	Sources: https://pubmed.ncbi.nlm.nih.gov/28417284 Page: p.4
90 mg 1 times / day multiple, oral MTD Dose: 90 mg, 1 times / day Route: oral Route: multiple Dose: 90 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24583798 Page: p.2448	unhealthy, ADULT n = 19 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 19 Sources: https://pubmed.ncbi.nlm.nih.gov/24583798 Page: p.2448	DLT: Skin rash, Electrocardiogram T wave inversion... Dose limiting toxicities: Skin rash (grade 3, 5.3%) Electrocardiogram T wave inversion (grade 3, 5.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/24583798 Page: p.2448
100 mg 1 times / day multiple, oral Studied dose Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24583798 Page: p.2447	unhealthy, ADULT n = 7 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/24583798 Page: p.2447	DLT: Skin rash, Dyskinesia... Dose limiting toxicities: Skin rash (grade 3, 14.3%) Dyskinesia (grade 2, 14.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/24583798 Page: p.2447
50 mg 2 times / day multiple, oral Studied dose Dose: 50 mg, 2 times / day Route: oral Route: multiple Dose: 50 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28417284 Page: p.4	unhealthy, ADULT n = 6 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/28417284 Page: p.4	DLT: Macular rash, Maculopapular rash... Dose limiting toxicities: Macular rash (grade 3, 16.7%) Maculopapular rash (grade 3, 16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/28417284 Page: p.4
70 mg 1 times / day multiple, oral Studied dose Dose: 70 mg, 1 times / day Route: oral Route: multiple Dose: 70 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28417284 Page: p.4	unhealthy, ADULT n = 6 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/28417284 Page: p.4	DLT: Fatigue... Dose limiting toxicities: Fatigue (grade 3, 33.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/28417284 Page: p.4

AEs

AE	Significance	Dose	Population
Hepatic enzyme increased	42.9%	120 mg 2 times / day multiple, oral Highest studied dose Dose: 120 mg, 2 times / day Route: oral Route: multiple Dose: 120 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24583798 Page: p.2447	unhealthy, ADULT n = 7 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/24583798 Page: p.2447
Decreased appetite	grade 3, 14.3% DLT	120 mg 2 times / day multiple, oral Highest studied dose Dose: 120 mg, 2 times / day Route: oral Route: multiple Dose: 120 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24583798 Page: p.2447	unhealthy, ADULT n = 7 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/24583798 Page: p.2447
Hypophosphatemia	grade 3, 14.3% DLT	120 mg 2 times / day multiple, oral Highest studied dose Dose: 120 mg, 2 times / day Route: oral Route: multiple Dose: 120 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24583798 Page: p.2447	unhealthy, ADULT n = 7 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/24583798 Page: p.2447
Fatigue	grade 3, 16.7% DLT	40 mg 2 times / day multiple, oral MTD Dose: 40 mg, 2 times / day Route: oral Route: multiple Dose: 40 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28417284 Page: p.4	unhealthy, ADULT n = 6 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/28417284 Page: p.4
Pruritic rash	grade 2, 8% DLT	50 mg 2 times / day multiple, oral MTD Dose: 50 mg, 2 times / day Route: oral Route: multiple Dose: 50 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24583798 Page: p.2447	unhealthy, ADULT n = 25 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 25 Sources: https://pubmed.ncbi.nlm.nih.gov/24583798 Page: p.2447
Electrocardiogram T wave inversion	grade 3, 5.3% DLT	90 mg 1 times / day multiple, oral MTD Dose: 90 mg, 1 times / day Route: oral Route: multiple Dose: 90 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24583798 Page: p.2448	unhealthy, ADULT n = 19 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 19 Sources: https://pubmed.ncbi.nlm.nih.gov/24583798 Page: p.2448
Skin rash	grade 3, 5.3% DLT	90 mg 1 times / day multiple, oral MTD Dose: 90 mg, 1 times / day Route: oral Route: multiple Dose: 90 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24583798 Page: p.2448	unhealthy, ADULT n = 19 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 19 Sources: https://pubmed.ncbi.nlm.nih.gov/24583798 Page: p.2448
Dyskinesia	grade 2, 14.3% DLT	100 mg 1 times / day multiple, oral Studied dose Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24583798 Page: p.2447	unhealthy, ADULT n = 7 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/24583798 Page: p.2447
Skin rash	grade 3, 14.3% DLT	100 mg 1 times / day multiple, oral Studied dose Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24583798 Page: p.2447	unhealthy, ADULT n = 7 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/24583798 Page: p.2447
Macular rash	grade 3, 16.7% DLT	50 mg 2 times / day multiple, oral Studied dose Dose: 50 mg, 2 times / day Route: oral Route: multiple Dose: 50 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28417284 Page: p.4	unhealthy, ADULT n = 6 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/28417284 Page: p.4
Maculopapular rash	grade 3, 16.7% DLT	50 mg 2 times / day multiple, oral Studied dose Dose: 50 mg, 2 times / day Route: oral Route: multiple Dose: 50 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28417284 Page: p.4	unhealthy, ADULT n = 6 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/28417284 Page: p.4
Fatigue	grade 3, 33.3% DLT	70 mg 1 times / day multiple, oral Studied dose Dose: 70 mg, 1 times / day Route: oral Route: multiple Dose: 70 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28417284 Page: p.4	unhealthy, ADULT n = 6 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/28417284 Page: p.4

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461 MRP1 106

Drug as perpetrator

Target	Modality	Activity
CYP3A4 1925	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=440681474	inconclusive [IC50 13.4504 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=440681474	no
P-gp 1650	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/29710665/ \| https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=363680715	yes [IC50 2.9093 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=440681474	yes [IC50 26.837 uM]
MRP1 172	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/29710665/	yes

PubMed

Title	Date	PubMed
Drug discovery approaches targeting the PI3K/Akt pathway in cancer.	2008 Sep 18	18794885

Patents

Sample Use Guides

In Vivo Use Guide

50 mg twice daily: no eating for 2 hours prior and 1 hour after dose

Route of Administration: Oral

In Vitro Use Guide

Voxtalisib treatment results in decreased cell viability in 13 PDA cell lines in a dose-dependent manner. 10uM induced approx. 40% apoptosis in BxPC-3 cells.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 01:46:06 UTC 2023` Edited by `admin` on `Sat Dec 16 01:46:06 UTC 2023`
Record UNII	CVL1685GPH
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

VOXTALISIB

Official Name

English

SAR-245409

Code

English

SAR245409

Code

English

PYRIDO(2,3-D)PYRIMIDIN-7(8H)-ONE, 2-AMINO-8-ETHYL-4-METHYL-6-(1H-PYRAZOL-3-YL)-

Systematic Name

English

XL-765

Code

English

2-AMINO-8-ETHYL-4-METHYL-6-(1H-PYRAZOL-3-YL)PYRIDO(2,3-D)PYRIMIDIN-

Systematic Name

English

2-AMINO-8-ETHYL-4-METHYL-6-(1H-PYRAZOL-5-YL)PYRIDO(2,3-D)PYRIMIDIN-7(8H)-ONE

Systematic Name

English

Voxtalisib [WHO-DD]

Common Name

English

voxtalisib [INN]

Common Name

English

VOXTALISIB [USAN]

Common Name

English

XL765

Code

English

2-Amino-8-ethyl-4-methyl-6-(1H-pyrazol-3-yl)pyrido[2,3-d]pyrimidin-7(8H)-one

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C129825